The Prognostic Significance of Elevated Cyclooxygenase-2 Expression in Patients with Adenocarcinoma of the Esophagus.
Abstracts
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Background: The use of NSAIDs is associated with a reduced risk of gastrointestinal cancer. Cyclooxygenase (COX) is the best-known target of NSAIDs, and expression of the inducible COX-2 isoform is elevated in adenocarinomas of the esophagus but its clinical significance remains unclear. We examined COX-2 expression in esophageal adenocarcinomas and its relation to prognosis. Methods: Tumor sections of 145 consecutive patients undergoing potentially curative surgery for an adenocarcinoma arising from a Barrett esophagus were immunohistochemically stained using a COX-2 specific anti-human monoclonal antibody. The specimens were scored based on the intensity and extent of COX-2 immunopositivity. We studied survival in relation to COX-2 expression and other prognostic factors. Results: COX-2 immunoreactivity was negative to weak in 21% (COX-2 Low) and moderate to strong in 79% (COX-2 High) of the tumors. Survival was significantly worse among patients with high COX-2 expression compared to COX-low patients (p=0.002, log rank test) with a 5-year survival rate of 35% and 70% respectively. Patients with high COX-2 expression were more likely to develop distant metastases (p=0.02) and local recurrences (p=0.05). The effect of COX-2 expression on survival was still present after adjustment of other prognostic factors. Conclusion: Elevated expression of COX-2 protein is associated with reduced survival of patients with esophageal adenocarcinoma. These findings support the effort to initiate clinical studies to the use of COX-2 inhibitors as a novel (adjuvant) chemotherapeutic modality for the treatment of esophageal adenocarcinoma. |
